A variety of proteomic techniques systematically identify the substrate target protein of the deuphinized enzyme USP14.

On November 13, Tan Minjia, a researcher at the Shanghai Institute of Pharmaceutical Research of the Chinese Academy of Sciences, worked with Li Xiaoying, a professor of endocrinology at Zhongshan Hospital at Fudan University, to publish a research paper entitled Proteome-wide analysis of USP14s sphonyd its, itis, in hepatosteasis, with a team of endocrinology and fassn.
the study systematically identified the substrate target protein of uphnophine USP14 through a variety of proteomic techniques, and further clarified the new mechanism of USP14 in the development of non-alcoholic fatty liver.
protein ubiquitination is one of the translation and post-translation modifications of proteins with important biological functions in the body. the dynamic balance of
ubiquitinization and de-ubiquitation in the body is a key mechanism for regulating protein degradation and maintaining the steady state of cytoproteins.
USP14 is one of the main transalinatinating enzymes (deubiquitining enzymes, DUBs) that binds to proteases, and it is now considered that its main function is to prevent the error of ubiquitinization of proteins in the body, thereby participating in the regulation of protein degradation process, and a number of studies have proved that it plays an important role in the regulation of nervous system function and the development of tumors, and there are several small molecular inhibitors targeted at this target for anti-tumor drug research and development. however,
, the regulatory substrate of USP14 is still very little known, whether it is involved in other physiological and pathological processes is still unclear, is one of the bottlenecks in the current USP14 research.
Tan Minjia's team and Li Xiaoying's team, through the combination of large-scale quantitative proteomics, ubiquitinal histology and protein-protein interaction histology and other proteomics techniques, combined with comprehensive analysis of bioinformatics, systematically identified the target protein of USP14.
study found that USP14 was involved in many previously undiscovered biological pathways, especially fatty acids and energy metabolism-related pathways. further data analysis and biochemical experiments
proved that fatty acid synth (FASN), the key enzyme in fatty acid synthesis pathways, is one of the target molecules of USP14.
through a series of gene silencing, knockout, and overexpression experiments, obese mice with increased expression through USP14 reduced FASN ubiquitin levels to improve their stability, resulting in an increase in triglyceride synthesis, and ultimately promote the development of non-alcoholic fatty liver.
the study reveals an important new mechanism for the development of ulycodone USP14 in the development of fatty liver and suggests that it may be a potential drug target for the treatment of fatty liver and related metabolic diseases. The co-authors of the
thesis are Liu Bin, a postdoctoral fellow at Shanghai Drug Institute, Jiang Shangwen, a graduate student, and Li Min, a graduate student at Zhongshan Hospital.
the paper co-authors are Tan Minjia of Shanghai Drug Institute, Li Xiaoying of Zhongshan Hospital and Lu Yan, a researcher.
research is funded by the Ministry of Science and Technology's "973" program, the National Natural Science Foundation's major research program, the national key research and development program, and the Lu Jiaxi International Team of the Chinese Academy of Sciences.
Source: Shanghai Institute of Pharmaceutical Research.